Thylakoids suppress appetite by increasing cholecystokinin resulting in lower food intake and body weight in high‐fat fed mice

Thylakoids are membranes isolated from plant chloroplasts which have previously been shown to inhibit pancreatic lipase/colipase catalysed hydrolysis of fat in vitro and induce short‐term satiety in vivo. The purpose of the present study was to examine if dietary supplementation of thylakoids could affect food intake and body weight during long‐term feeding in mice. Female apolipoprotein E‐deficient mice were fed a high‐fat diet containing 41% of fat by energy with and without thylakoids for 100 days. Mice fed the thylakoid‐enriched diet had suppressed food intake, body weight gain and body fat compared with the high‐fat fed control mice. Reduced serum glucose, serum triglyceride and serum free fatty acid levels were found in the thylakoid‐treated animals. The satiety hormone cholecystokinin was elevated, suggesting this hormone mediates satiety. Leptin levels were reduced, reflecting a decreased fat mass. There was no sign of desensitization in the animals treated with thylakoids. The results suggest that thylakoids are useful to suppress appetite and body weight gain when supplemented to a high‐fat food during long‐term feeding. Copyright © 2009 John Wiley & Sons, Ltd.     

Bioequivalence, pharmacokinetic and pharmacodynamic response to combined extended release formulations of felodipine and metoprolol in healthy volunteers

Objective: The primary aim of this study was to investigate whether bioequivalence is achieved for a new fixed combination of extended-release (ER) felodipine and controlled-release (CR/ZOK) metoprolol␣compared with the free combination of felodipine ER metoprolol CR/ZOK. The second aim was to study whether there was an interaction in pharmacokinetics and pharmacodynamics between felodipine and metoprolol when administered as ER formulation. Methods: Two four-way cross-over studies were performed in 36 young subjects and 24 elderly subjects with frequent measurement of drug plasma concentrations, blood pressures and heart rate. The pharmacokinetic analysis included enantioselective analysis in six subjects. Results: Bioequivalence between the fixed combination and the free combination was observed for the two drugs (mean difference 27%) except for a minor deviation regarding C_max of metoprolol in the elderly. No significant interaction was shown except for a small increase (6%) of metoprolol AUC in the younger subjects. Mean plasma S-/R-enantiomer ratios were almost identical for the different treatments. Blood pressure and heart rate was significantly reduced for the fixed combination compared with felodipine ER in the younger and the elderly subjects. No significant difference regarding pharmacodynamics was detected between the fixed combination and the corresponding free combination. Conclusion: The fixed combination consistently provides fairly constant and effective felodipine and metoprolol concentrations after once-daily administration of one tablet. It is clinically interchangeable with the free combination of metoprolol CR/ZOK tablets and felodipine ER tablets. Finally, felodipine and metoprolol do not interact on a pharmacokinetic level when administered as the fixed combination. Received: 29 October 1996 / Accepted in revised form: 21 March 1997     

Treatment for “Helpless” Women Suffering from Chronic Spinal Pain: A Randomized Controlled 18-Month Follow-Up Study

This prospective randomized controlled outcome study was designed to evaluate whether a MultiModal Cognitive—Behavioral Treatment for chronic spinal pain (MMCBT) specifically designed for women has an increased effect on well being and return to work compared to a regular MMCBT regimen. In Sweden, spinal pain is most prevalent among women. A tremendous amount of money is spent on secondary prevention of spinal pain. Yet, little is known about the effect of the interventions. A need for well designed outcome studies exist. Fifty-four subjects from a cohort of all registered sick-listed women in three districts of Stockholm participated in the study. Subjects were allocated by central randomization into two groups. One group was treated with a regular MMCBT program and the other group with a MMCBT program specifically designed for women. Assessments were performed at pretreatment–posttreatment (last treatment day) and at 6 and 18 months posttreatment. Questionnaires covering the bio-psycho-social spectra of the chronic pain syndrome, and sick leave were used to measure outcome. Intention to treat and true to protocol analyses were performed. The only significant differences found between groups were improvements in self-reported disability and in coping with pain, favoring the experimental treatment. About one-third of the variance in disability was explained by the set of pain-coping strategies assessed in the study. The results do not lend sufficient statistical support to warrant acceptance of the experimental treatment as superior to the regular treatment in improving health and sick leave. Further investigation with larger groups is needed before a solid scientific conclusion can be drawn.     

Natural killer cell activity and CSF monoamine metabolites in suicide attempters

The aim of this study was to investigate markers of serotonin and immune function in suicidal patients. Cytotoxic activity of natural killer cells (NK) and CD16 lymphocytes were studied in 28 suicide attempters and 26 healthy controls, and related in patients to 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF). Patients with CSF 5-HIAA below the median had significantly lower NK cell activity than other patients. CD16 cell frequency was significantly lower in patients than in controls, and patients also tended to have lower NK cell cytotoxicity than healthy controls. There were no statistically significant correlations between 4-hydroxy-3methoxyphenyl glycol (HMPG), homovanillic acid (HVA), CSF cortisol and NK cell activity. The results support the hypothesis of compromised immune function in suicidal patients with evidence of disordered serotonin function.     

Mammographic growth rate, DNA ploidy, and S-phase fraction analysis in breast carcinoma. A prognostic evaluation in a screened population.

BACKGROUND. The authors examined prognostic factors in 158 cases of breast carcinoma with known mammographic tumor volume doubling times (DT). METHODS. The tumors were retrospectively reexamined histologically and flow cytometric analysis of DNA ploidy and S-phase fraction (SPF) was performed on archival paraffin-embedded material in each case. Life tables and Cox multivariate analyses were used for statistical evaluation of prognostic factors. RESULTS. In univariate analysis of survival data, clinical and pathologic stage, histologic grade, the presence of axillary lymph node metastases, and SPF were significant prognostic predictors, but mammographic DT and DNA ploidy were not. SPF also contributed prognostic information in the subgroup of carcinoma cases detected by screening. In a Cox multivariate analysis, SPF, the presence of axillary lymph node metastases, and Stage II-III disease (as opposed to Stage I disease) were independent significant predictors of survival. In univariate analyses of distant disease-free survival, clinical and pathologic stage, tumor size, histologic grade, the presence of involved axillary nodes, DT, and SPF all were significant prognostic factors. CONCLUSIONS. SPF, stage, and lymph node status were important prognostic factors in this patient material with predominantly small and node-negative breast carcinomas, whereas DNA ploidy and mammographic DT provided less prognostic information. The prognosis of carcinoma detected during screening did not differ significantly from that of breast carcinoma discovered otherwise in this selected patient group.     

Ethical Reasoning Among Registered Nurses Experienced in Dementia Care

Abstract. Registered nurses regarded as “experienced and good” in dementia care were interviewed about the feeding of a severely demented patient who showed refusal-like feeding behaviour. Not one of the twenty nurses could see herself using force against her patients. Most interviewees justified their decisions to feed a severely demented patient and answered questions about whether they would change their minds if there were certain circumstances in terms of words that could be interpreted as referring to the ethical principle of beneficence. The nurses stressed the difficulty to understand the meaning of severely demented patients' feeding behaviour and decide when force-feeding occurs. When asked to rank ethical principles of importance for the decision, however, the most common answer was that they would give priority to the ethical principle of autonomy. The nurses did not see the ethical principles as separate entities, that could be applied one by one, but tried to integrate them into a whole. The findings of this study were interpreted as indicating that principled ethics is not an adequate model to describe experienced nurses' ethical reasoning.